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Leukemic presentation in nodal mantle cell lymphoma is characterized by frequent SOX11 negativity, a poor risk genomic landscape including higher alterations, and worse overall survival.
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Hematopathology Service, Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
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View Article and Find Full Text PDFTP53-Mutated Myeloid Neoplasms: 2024 Update on Diagnosis, Risk-Stratification, and Management.
Am J Hematol
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Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, South Australia, Australia.
Alterations in the tumor suppressor gene TP53 are common in human cancers and are associated with an aggressive nature. Approximately 8%-12% of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) harbor TP53 mutations (TP53) and present immense challenges due to inherent chemoresistance and poor outcomes. As TP53 are more common in older individuals and those with secondary/therapy-related myeloid neoplasms (MN), their incidence is expected to increase with an aging population and rising proportion of cancer survivors.
View Article and Find Full Text PDFRapid Development of Unclassified Myeloid Lineage Acute Leukaemia With Trisomy 6 and U2AF1 Mutation.
J Cell Mol Med
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Faculty of Medicine, Division of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland.
We present a case of acute clonal bone marrow 98% infiltration of atypical myeloid cells with borderline hypogranular/agranular promyelocytes/myelocytes and occasional blast cells maturity, which also formed extramedullary tumours in the chest wall, with isolated trisomy of chromosome 6 and pathogenic variant U2AF1 (S34F) that escapes established acute myeloid leukaemia (AML) diagnostic criteria according to the World Health Organization (WHO) classification. Following standard daunorubicin and cytarabine induction therapy, the disease progressed with the appearance of a previously undetected clone of leukaemic cells with a distinct immunophenotype demonstrating monocytoid differentiation and clonal evolution to a hypo-tetraploid karyotype with an average number of 84 chromosomes and new pathogenic NRAS and ZRSR2 mutations. The patient reactivated refractory disseminated intravascular coagulation (DIC) leading to a progressive supratentorial hematoma and finally cardiac arrest.
View Article and Find Full Text PDFTargeting the Immune Microenvironment in Chronic Lymphocytic Leukemia: An Evolving Therapeutic Strategy.
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AstraZeneca, Gaithersburg, USA.
Although small molecule inhibitors that target the aberrant signaling pathways and molecular defects of chronic lymphocytic leukemia (CLL) result in improved survival benefits vs. traditional chemoimmunotherapy or chemotherapy, treatment resistance may result later, reflecting the intrinsic tumor heterogeneity, persistence of the leukemic clone, and presence of the tumor microenvironment, which supports the survival of the disease clone. Patients with CLL have immune-related abnormalities in T lymphocyte subset composition, immune synapse formation, and other immune dysregulations.
View Article and Find Full Text PDFTargeted Therapies in Myelofibrosis: Present Landscape, Ongoing Studies, and Future Perspectives.
Am J Hematol
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Department of Experimental and Clinical Medicine, CRIMM, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliero- Universitaria Careggi, University of Florence, Florence, Italy.
Myelofibrosis (MF) is a myeloproliferative neoplasm that is accompanied by driver JAK2, CALR, or MPL mutations in more than 90% of cases, leading to constitutive activation of the JAK-STAT pathway. MF is a multifaceted disease characterized by trilineage myeloid proliferation with prominent megakaryocyte atypia and bone marrow fibrosis, as well as splenomegaly, constitutional symptoms, ineffective erythropoiesis, extramedullary hematopoiesis, and a risk of leukemic progression and shortened survival. Therapy can range from observation alone in lower-risk and asymptomatic patients to allogeneic hematopoietic stem cell transplantation, which is the only potentially curative treatment capable of prolonging survival, although burdened by significant morbidity and mortality.
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